This project aims to characterize the formation and repair of DNA damage after treatment of mammalian cells with antitumor agents and to correlate the effects on DNA with cell killing. In addition to standard techniques of DNA analysis, this work entails the development of a new set of techniques based on the DNA alkaline elution principle. During the past year several advances were made of which the following are most notable: (1) A method of quantitation of DNA-protein crosslinks has been devised and applied to trans-Pt(II) complex and X-ray. (2) A new type of drug-effect on DNA, consisting of protein-associated DNA single-strand breaks, was discovered in cells treated with DNA intercalating agents (e.g., adriamycin and ellipticine). (3) Two different classes of DNA crosslinks were observed in cells treated cis-Pt(II) and trans-Pt(II) complexes.